Date of Award
Doctor of Philosophy
Kindling is an example of permanent change in brain function that results from repeated elicitation of epileptiform neural activity. The molecular/genetic mechanisms by which kindling is produced and maintained are just beginning to be addressed. Recently two proto-oncogenes, c-fos and c-Ha-ras, have been identified as possible mediators of intracellular signal transduction and may mediate the kindling process. Additionally, c-fos, has been proposed as the gene responsible for turning on molecular events that might underlie the long-term neural changes that occur during kindling. The objective of the present study was to: (i) further investigate the enhancement of c-fos and c-Ha-ras levels following kindled seizures and (ii) investigate the role of c-fos in the plastic changes underlying kindling.;In this study, male hooded rats, were electrically kindled and the resulting c-fos and c-Ha-ras gene expression was quantified using Northern blot analysis. The results indicated that: (i) c-fos was constitutively expressed in forebrain and cerebellum, (ii) basal levels of c-fos were equivalent in naive and in fully kindled rats that has been seizure free for 3 weeks, (iii) an amygdala-pyriform kindled seizure massively and transiently increased c-fos levels, (iv) kindled seizure enhancement of c-fos was observed throughout forebrain and cerebellum, (v) enhancement of AD duration corresponded to enhanced c-fos levels, (vi) enhanced c-fos levels were observed in the amygdala-pyriform contralateral to the kindled site, and the enhancement did not depend on the occurrence of Ad in the contralateral amygdala-pyriform, (vii) electrical stimulations not resulting in AD increased c-fos levels, (viii) c-fos levels were increased by control stimulation, (ix) c-fos induction was partially refractory, (x) PTZ caused c-fos induction independent of a motor convulsion, and (xi) kindled seizures did not alter the expression of c-Ha-ras.;The most parsimonious explanation that accounts for the observations made in this study is that c-fos was expressed simply as a consequence of neural activity and not exclusively due to the specific neural activity (afterdischarge) required for kindling.
Teskey, G Campbell, "Expression Of The Proto-oncogene C-fos Following Electrical Kindling In The Rat" (1990). Digitized Theses. 1908.